Ammonia is a toxic waste by-product of cell metabolism which, as it accumulates in an aqueous cell-growth medium during the culturing of mammalian cells, inhibits cell growth and production of desired end products. A number of efforts have been made to solve this problem.
Currently, the aqueous cell growth medium with inhibitory levels of ammonia is simply discarded and replaced with fresh medium. This is inefficient as it requires additional equipment for sterilization and storage of fresh medium as well as the attendant replacement of costly serum in the fresh medium. Another proposed solution to the problem of ammonia accumulation has been the selection and use of a cell line that is more resistant to ammonia. See Ono et al., 94 J. Biochem 1493 (1983). However, there are relatively few cell lines that are known to be resistant to the inhibitory effects of ammonia. A more recent strategy for dealing with ammonia build-up has been strict control of glutamine (a primary source of ammonia) in the culture medium. See Glacken et al., 6 Bio/Technology 1041 (1988). However, this method only reduced ammonia by 25-30%, while compromising the ability of the cells to use other essential amino acids.
What is needed therefore, is a method of removing ammonia from mammalian cell cultures that dispenses with replacement of medium and glutamine control, and that may be utilized with the known wide variety of existing cell lines.